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14/10/2011 Muscle Dr Sarah Harney Department of Physiology [email protected] • How is muscle tissue organised? • How do muscles contract? • How does muscle store/use energy? • What changes occur in muscle with use/disuse? 1 14/10/2011 Functions of Muscle Contraction • Controlled muscle contraction allows – Purposeful movement of the whole body or parts of the body – Manipulation of external objects – Propulsion of contents through various hollow internal organs – Emptying of contents of certain organs to external environment Chapter 8 Muscle Physiology Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Muscle Tissue • Comprises largest group of tissues in body • Three types of muscle – Skeletal muscle • Make up muscular system – Cardiac muscle • Found only in the heart – Smooth muscle • Appears throughout the body systems as components of hollow organs and tubes • Classified in two different ways – Striated or unstriated – Voluntary or involuntary 2 14/10/2011 3 Muscle Types Categorization of Muscle 3 14/10/2011 How does skeletal muscle contract? • Structure • Changes in Protein arrangements Structure of Skeletal Muscle • Muscle consists a number of muscle fibers lying parallel to one another and held together by connective tissue • Single skeletal muscle cell is known as a muscle fiber – Multinucleated – Large, elongated, and cylindrically shaped – Fibers usually extend entire length of muscle 4 14/10/2011 Structure of Skeletal Muscle • Myofibrils – Contractile elements of muscle fiber – Regular arrangement of thick and thin filaments • Thick filaments – myosin (protein) • Thin filaments – actin (protein) – Viewed microscopically myofibril displays alternating dark (the A bands) and light bands (the I bands) giving appearance of striations Muscle fiber myofibril Chapter 8 Muscle Physiology Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning 5 14/10/2011 Structure of Skeletal Muscle • Sarcomere – Functional unit of skeletal muscle – Found between two Z lines (connects thin filaments of two adjoining sarcomeres) – Regions of sarcomere • A band – Made up of thick filaments (Myosin) along with portions of thin filaments that overlap on both ends of thick filaments • I band – Consists of remaining portion of thin filaments (Actin) that do not project into A band Structure of Skeletal Muscle Sarcomere Chapter 8 Muscle Physiology Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning 6 14/10/2011 Changes in Banding Pattern During Shortening Sliding filament model of contraction Thick and thin filaments do not change length during contraction but overlap to reduce sarcomere length 7 14/10/2011 A number of Proteins are Essential for Muscle Contraction Thick filaments • Myosin Thin filaments • Actin • Troponin • Tropomysin Role of Calcium in Cross-Bridge Formation 8 14/10/2011 Cross bridge cycling requires Ca2+ release from intracellular stores and ATP Ca2+ released from intracellular stores binds to troponin, allowing actin to interact with myosin Adenosine triphosphate (ATP) is the energy source for all cells of the body. Nutrients – glucose- are converted to ATP and energy is stored in the high energy phosphate bonds of ATP. Breakdown of ATP to ADP releases energy which is used by the cell ATP ADP + inorganic phosphate (Pi) ATP binding to myosin is required for cross bridge detachment and priming for subsequent cross-linking. Following death, the absence of ATP prevents cross bridge detachment, causing rigor mortis Smooth muscle 9 14/10/2011 Smooth muscle No z-lines, therefore actin is anchored to dense bodies, made of same protein as z-lines in skeletal muscle Cardiac Muscle Chapter 8 Muscle Physiology Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning 10 14/10/2011 Smooth Muscles: Contrasted to Skeletal Muscle • Homeostatic role – Control fluid – Sphincters • Tonic contractions – Support tubes – Move products • Slow contractions – Little fatigue – Low O2 use Figure 12-24: Duration of muscle contraction in three types of muscle Motor Unit Recruitment • A single muscle is innervated by multiple motor neurons • Each motor neuron innervates a number of muscle fibres, but each muscle fibre receives input from only one motor neuron • The muscle fibres activated simultaneously by the same motor neuron are known as a motor unit 11 14/10/2011 The synapse between motor neurons and skeletal muscle is The Neuromuscular Junction (NMJ) 1. Action potential propagated to motor neuron axon terminal 2. Depolarization of voltagegated Ca2+ channels 3. Increase in Ca2+ triggers release of Acetylcholine 4. Acetylcholine diffuses across junction, binds to and opens Ach receptor channels 5. Na+ enters muscle cell motor end plate, depolarizing the cell Acetylcholine is the Neurotransmitter at the NMJ Motor neuron endplates on skeletal muscle • Acetylcholine (Ach) is released by motor neuron axon terminals • Binds to nicotinic Ach receptors on skeletal muscle tissue • Depolarization (positive change in membrane potential) results in muscle contraction 12 14/10/2011 Agents that block or modify activity at the NMJ • ACh receptors are blocked by organophosphate poisons – used as pesticides (malathion) or nerve gas (sarin) • In the autoimmune disease myasthenia gravis, antibodies to the ACh receptors block Ach binding, causing muscle weakness • Botulinum toxin (Botox) blocks Ach release at the NMJ – can be fatal in Botulism (due to inhibition of breathing) but is used clinically to relax muscles in spasm and for cosmetic purposes Motor Unit Recruitment • Motor unit – One motor neuron and the muscle fibers it innervates • Number of muscle fibers varies among different motor units • Number of muscle fibers per motor unit and number of motor units per muscle vary widely – Muscles that produce precise, delicate movements contain fewer fibers per motor unit, e.g. fingers – 1 nerve to 1 muscle fibre, finely controlled movement – Muscles performing powerful, coarsely controlled movement have larger number of fibers per motor unit, e.g. leg muscles -1 nerve to 2000 muscle fibres, large increases in muscle tension 13 14/10/2011 Summation and Tetanus •During a single stimulus, twitch, released Ca2+ allows cross-bridge formation and muscle contraction • Following initial stimulus Ca2+ is pumped back into intracellular stores • Prolonged stimulation elevated intracellular Ca 2+, all cross bridges are formed and the muscle reaches maximal tension, known as tetanus Muscle Tension • Tension is produced internally within muscle • Tension must be transmitted to bone by means of connective tissue and tendons before bone can be moved (series-elastic component) • Muscle typically attached to at least two different bones across a joint: Origin End of muscle attached to more stationary part of skeleton Insertion End of muscle attached to skeletal part that moves 14 14/10/2011 Physics of Joint Movement • Bones, muscles, and joints interact to form lever systems • Muscles: contraction force – Isotonic: ‘constant tension’, used for body movements and moving objects – Isometric: ‘constant length’, no movement, used for maintaining posture and for supporting objects in a fixed position Muscle contraction 15 14/10/2011 Skeletal Muscle Metabolism Alternative pathways for production of ATP Muscle glycogen • Glycolysis can lead to the formation of lactate during conditons of limited O2 supply, i.e. during high intensity activity Glucose Glycolysis ATP No O2 (anaerobic) Lactate Pyruvate Oxidative Phosphorylation O2 (aerobic) ATP CO2 H2O • Lactate accumulation causes muscle burn during activity • Oxidative phosphorylation requires O2 and yields more ATP but is relatively slow and is utilised more during slower, endurance activity Chapter 8 Muscle Physiology Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Muscle cells can also store energy as creatine phosphate • Cellular creatine phosphate stores are used in the first minute of intense activity Creatine phosphate + ADP Creatine kinase Creatine + ATP • Creatine is obtained in dietary protein • Creatine supplements are commonly used by athletes, however the benefits are risks of long-term use are not established • Some evidence of liver/kidney problems, not conclusive • Supplements may be beneficial for patients with muscular dystrophy, age-related muscle wasting or diseases such as Parkinson’s 16 14/10/2011 Fast and Slow Muscle Fibre Types Type I Slow twitch fibres Type II Fast twitch fibres (Type IIa and Type IIb, use different mechanisms for ATP generation) Proportions of type I and type II fibres: • vary between muscle types, e.g. more slow twitch fibres in muscles used for low-intensity activity, such as the legs and more fast twitch fibres in muscles used for fast movements, such as the biceps • is genetically determined Sprint athletes – more fast twitch fibres Endurance athletes – more slow twitch fibres Muscle Fatigue • Occurs when exercising muscle can no longer respond to stimulation with same degree of contractile activity • Defense mechanism that protects muscle from reaching point at which it can no longer produce ATP • Underlying causes of muscle fatigue are unclear, most likely relate to build up of metabolic byproducts such as inorganic phosphate, lactate, excess K+ or depletion of energy stores 17 14/10/2011 Central Fatigue • Occurs when CNS no longer adequately activates motor neurons supplying working muscles • Often psychologically based • Mechanisms involved in central fatigue are poorly understood Adaptive changes in Muscle Hypertrophy • High intensity resistance training results in increased muscle mass, due to increased fast twitch fibres • Increased synthesis of myosin and actin filaments resulting in greater contractile strength Sex differences in skeletal muscle mass: 42 % of body mass in males 36 % of body mass in females • Testosterone and similar androgen steroid hormones stimulate myosin and actin synthesis • Steroid abuse associated with many cardiovascular, reproductive and psychological side effects 18 14/10/2011 Adaptive changes in Muscle Atrophy • Reduced muscle mass associated with lack of use • Can occur when nerve supply is intact but muscle not used e.g. during recovery from a broken bone • May result from loss of nerve stimulation following injury • Electrical muscle stimulation (EMS) may be useful in patients with chronic illness or for recovering function after stroke • Some models of EMS developed by NASA as astronauts suffer muscle atrophy after long periods of zero gravity From: Sheffler and Chae, Muscle and Nerve (2007) 35: 562-590 Reanimating Limbs After Disease Richard B. Stein and Vivian Mushahwar Review TRENDS in Neurosciences Vol.28 No.10 October 2005 Intact muscle not receiving input due to CNS disease 19 14/10/2011 Use of Electrical Muscle Stimulation after Spinal cord Injury Figure 1 | Brain-controlled functional electrical stimulation (FES) of muscle. a, Schematic shows cortical cell activity converted to FES during peripheral nerve block. b, Example of motor cortex cell activity controlling FES of paralysed wrist extensors. Extensor (red shading) and centre (grey shading) wrist torque targets were randomly presented. Monkeys learned to modulate smoothed cell rate to control proportional muscle stimulation. FES was delivered to muscles EDC and ED4,5 at 50 s21, with current proportional to cell rate above a stimulation threshold (0.4mApps213[cell rate216 pps]; #10 mA). Here pps indicates pulses per second. c, Histograms of cell rates while acquiring the extensor and centre targets, illustrating cell activity used to successfully control FES. Shading indicates target hold period and horizontal line denotes baseline cell rate. Moritz et al. (2008) Direct control of paralysed muscles by cortical neurons. Nature 456, 639-642 20